CHO mutants, resistant to over 100-fold of a normally toxic level of extracellular cadmium have been used to examine the mutually antagonistic effect of Cd and Zn on their uptake. Cadmium uptake in these mutants is only 7-10% that of the parental cells. Zinc uptake in these mutants is equal to or greater than that in the wild-type cells. Results of kinetic studies on uptake indicated that the two metals interact by competitive inhibition. TheK m andK i values for Cd and/or Zn were different in some of the mutants and indicate multiple carriers may be involved in the transport of these metals. The reduction in Cd uptake and concomitant increase in Zn uptake contribute to the increased Cd resistance in these mutants.